The main objectives are to search for the biosynthesis of tetrahydroisoquinoline (TIQ) alkaloids in animals and in man during ethanol intoxication and to delineate some of their pharmacologic properties. TIQ alkaloids arise as condensation products of catecholamines (such as dopamine, norepinephrine and epinephrine) with acetaldehyde, which is a metabolite of ethanol. Other experiments are conducted with methanol, which gives rise in vivo to formaldehyde and, in turn, to another series of TIQ alkaloids. We are interested in the potential pharmacologic actions of biosynthesized TIQ alkaloids: Do they provoke changes in neuronal function and changes in behavior during and after the ingestion of alcoholic beverages? We are also considering the possibility that TIQ alkaloids may play a role in the addictive phase of alcoholism. We plan to label the brain and sympathetic nervous system of rats by neuronal uptake of radioactive H3-catecholamines. We will then look for the synthesis of H3-TIQ alkaloids in inebriated animals. Tissues will be analyzed by thin-layer chromatography followed by scintillation spectrometry. Second, we will evaluate whether the nervous system can be labeled in vivo with H3-TIQ alkaloids; uptake and storage would favor a transmitter role for biosynthesized alkaloids. Third, the formaldehyde-derived alkaloids will be studied in tissues by a fluorescence microscopy method; these alkaloids may play a role in methanol intoxication and methanol poisoning. Fourth, we have previously observed that salsolinol (dopamine-acetaldehyde TIQ) blocks catecholamine uptake and releases catecholamines from rat brain synaptosomes in vitro. We will attempt to evaluate whether TIQ alkaloids play similar roles in vivo and whether or not these may be contributory to the responses to ingested alcoholic beverages.